OBJECTIVE: Elucidation of hepato-biliary mechanisms for dealing with xenobiotics, including drugs and chemical carcinogens. Specifically, uptake, binding and biliary excretion are investigated, as well as the interrelationships between these functions. The mechanism of chemically induced liver growth is also dealt with using nafenopin. This drug, in addition to altering biliary function, has a marked hepatomegalic effect. METHODS: Various xenobiotics are injected into rats and the plasma disappearance, liver uptake and binding, metabolism and biliary excretion are measured. The capacity to metabolize these xenobiotics is also assessed in vitro using liver microsomal preparations. Rates of formation of various metabolites are compared with their rates of biliary excretion and the rate-controlling step(s) in the overall hepato-biliary process is determined. The biochemical mechanisms underlying nafenopin-induced liver growth will be determined and compared to "physiological" mechanisms associated with the regenerating liver. A possible role for adrenergic mechanisms has been implied in previous work and will be pursued. Nafenopin will be administered to rats and the effects will be measured on RNA, DNA and protein synthesis, ornithine decarboxylase, amino acid uptake and levels of cyclic nucleotides. In addition, the influence of adrenergic blocking agents on each of these parameters will be determined.